@phdthesis{7525, abstract = {The medial habenula (MHb) is an evolutionary conserved epithalamic structure important for the modulation of emotional memory. It is involved in regulation of anxiety, compulsive behavior, addiction (nicotinic and opioid), sexual and feeding behavior. MHb receives inputs from septal regions and projects exclusively to the interpeduncular nucleus (IPN). Distinct sub-regions of the septum project to different subnuclei of MHb: the bed nucleus of anterior commissure projects to dorsal MHb and the triangular septum projects to ventral MHb. Furthermore, the dorsal and ventral MHb project to the lateral and rostral/central IPN, respectively. Importantly, these projections have unique features of prominent co-release of different neurotransmitters and requirement of a peculiar type of calcium channel for release. In general, synaptic neurotransmission requires an activity-dependent influx of Ca2+ into the presynaptic terminal through voltage-gated calcium channels. The calcium channel family most commonly involved in neurotransmitter release comprises three members, P/Q-, N- and R-type with Cav2.1, Cav2.2 and Cav2.3 subunits, respectively. In contrast to most CNS synapses that mainly express Cav2.1 and/or Cav2.2, MHb terminals in the IPN exclusively express Cav2.3. In other parts of the brain, such as the hippocampus, Cav2.3 is mostly located to postsynaptic elements. This unusual presynaptic location of Cav2.3 in the MHb-IPN pathway implies unique mechanisms of glutamate release in this pathway. One potential example of such uniqueness is the facilitation of release by GABAB receptor (GBR) activation. Presynaptic GBRs usually inhibit the release of neurotransmitters by inhibiting presynaptic calcium channels. MHb shows the highest expression levels of GBR in the brain. GBRs comprise two subunits, GABAB1 (GB1) and GABAB2 (GB2), and are associated with auxiliary subunits, called potassium channel tetramerization domain containing proteins (KCTD) 8, 12, 12b and 16. Among these four subunits, KCTD12b is exclusively expressed in ventral MHb, and KCTD8 shows the strongest expression in the whole MHb among other brain regions, indicating that KCTD8 and KCTD12b may be involved in the unique mechanisms of neurotransmitter release mediated by Cav2.3 and regulated by GBRs in this pathway. In the present study, we first verified that neurotransmission in both dorsal and ventral MHb-IPN pathways is mainly mediated by Cav2.3 using a selective blocker of R-type channels, SNX-482. We next found that baclofen, a GBR agonist, has facilitatory effects on release from ventral MHb terminal in rostral IPN, whereas it has inhibitory effects on release from dorsal MHb terminals in lateral IPN, indicating that KCTD12b expressed exclusively in ventral MHb may have a role in the facilitatory effects of GBR activation. In a heterologous expression system using HEK cells, we found that KCTD8 and KCTD12b but not KCTD12 directly bind with Cav2.3. Pre-embedding immunogold electron microscopy data show that Cav2.3 and KCTD12b are distributed most densely in presynaptic active zone in IPN with KCTD12b being present only in rostral/central but not lateral IPN, whereas GABAB, KCTD8 and KCTD12 are distributed most densely in perisynaptic sites with KCTD12 present more frequently in postsynaptic elements and only in rostral/central IPN. In freeze-fracture replica labelling, Cav2.3, KCTD8 and KCTD12b are co-localized with each other in the same active zone indicating that they may form complexes regulating vesicle release in rostral IPN. On electrophysiological studies of wild type (WT) mice, we found that paired-pulse ratio in rostral IPN of KCTD12b knock-out (KO) mice is lower than those of WT and KCTD8 KO mice. Consistent with this finding, in mean variance analysis, release probability in rostral IPN of KCTD12b KO mice is higher than that of WT and KCTD8 KO mice. Although paired-pulse ratios are not different between WT and KCTD8 KO mice, the mean variance analysis revealed significantly lower release probability in rostral IPN of KCTD8 KO than WT mice. These results demonstrate bidirectional regulation of Cav2.3-mediated release by KCTD8 and KCTD12b without GBR activation in rostral IPN. Finally, we examined the baclofen effects in rostral IPN of KCTD8 and KCTD12b KO mice, and found the facilitation of release remained in both KO mice, indicating that the peculiar effects of the GBR activation in this pathway do not depend on the selective expression of these KCTD subunits in ventral MHb. However, we found that presynaptic potentiation of evoked EPSC amplitude by baclofen falls to baseline after washout faster in KCTD12b KO mice than WT, KCTD8 KO and KCTD8/12b double KO mice. This result indicates that KCTD12b is involved in sustained potentiation of vesicle release by GBR activation, whereas KCTD8 is involved in its termination in the absence of KCTD12b. Consistent with these functional findings, replica labelling revealed an increase in density of KCTD8, but not Cav2.3 or GBR at active zone in rostral IPN of KCTD12b KO mice compared with that of WT mice, suggesting that increased association of KCTD8 with Cav2.3 facilitates the release probability and termination of the GBR effect in the absence of KCTD12b. In summary, our study provided new insights into the physiological roles of presynaptic Cav2.3, GBRs and their auxiliary subunits KCTDs at an evolutionary conserved neuronal circuit. Future studies will be required to identify the exact molecular mechanism underlying the GBR-mediated presynaptic potentiation on ventral MHb terminals. It remains to be determined whether the prominent presence of presynaptic KCTDs at active zone could exert similar neuromodulatory functions in different pathways of the brain. }, author = {Bhandari, Pradeep}, issn = {2663-337X}, keywords = {Cav2.3, medial habenula (MHb), interpeduncular nucleus (IPN)}, pages = {79}, publisher = {Institute of Science and Technology Austria}, title = {{Localization and functional role of Cav2.3 in the medial habenula to interpeduncular nucleus pathway}}, doi = {10.15479/AT:ISTA:7525}, year = {2020}, } @article{7534, abstract = {In the past two decades, our understanding of the transition to turbulence in shear flows with linearly stable laminar solutions has greatly improved. Regarding the susceptibility of the laminar flow, two concepts have been particularly useful: the edge states and the minimal seeds. In this nonlinear picture of the transition, the basin boundary of turbulence is set by the edge state's stable manifold and this manifold comes closest in energy to the laminar equilibrium at the minimal seed. We begin this paper by presenting numerical experiments in which three-dimensional perturbations are too energetic to trigger turbulence in pipe flow but they do lead to turbulence when their amplitude is reduced. We show that this seemingly counterintuitive observation is in fact consistent with the fully nonlinear description of the transition mediated by the edge state. In order to understand the physical mechanisms behind this process, we measure the turbulent kinetic energy production and dissipation rates as a function of the radial coordinate. Our main observation is that the transition to turbulence relies on the energy amplification away from the wall, as opposed to the turbulence itself, whose energy is predominantly produced near the wall. This observation is further supported by the similar analyses on the minimal seeds and the edge states. Furthermore, we show that the time evolution of production-over-dissipation curves provides a clear distinction between the different initial amplification stages of the transition to turbulence from the minimal seed.}, author = {Budanur, Nazmi B and Marensi, Elena and Willis, Ashley P. and Hof, Björn}, issn = {2469-990X}, journal = {Physical Review Fluids}, number = {2}, publisher = {American Physical Society}, title = {{Upper edge of chaos and the energetics of transition in pipe flow}}, doi = {10.1103/physrevfluids.5.023903}, volume = {5}, year = {2020}, } @article{7540, abstract = { In vitro propagation of the ornamentally interesting species Wikstroemia gemmata is limited by the recalcitrance to form adventitious roots. In this article, two strategies to improve the rooting capacity of in vitro microcuttings are presented. Firstly, the effect of exogenous auxin was evaluated in both light and dark cultivated stem segments and also the sucrose-content of the medium was varied in order to determine better rooting conditions. Secondly, different spectral lights were evaluated and the effect on shoot growth and root induction demonstrated that the exact spectral composition of light is important for successful in vitro growth and development of Wikstroemia gemmata. We show that exogenous auxin cannot compensate for the poor rooting under unfavorable light conditions. Adapting the culture conditions is therefore paramount for successful industrial propagation of Wikstroemia gemmata. }, author = {Verstraeten, Inge and Buyle, H. and Werbrouck, S. and Van Labeke, M.C. and Geelen, D.}, issn = {2223-8980}, journal = {Israel Journal of Plant Sciences}, number = {1-2}, pages = {16--26}, publisher = {Brill}, title = {{In vitro shoot growth and adventitious rooting of Wikstroemia gemmata depends on light quality}}, doi = {10.1163/22238980-20191110}, volume = {67}, year = {2020}, } @article{7541, abstract = {Semiconductor nanowires have been playing a crucial role in the development of nanoscale devices for the realization of spin qubits, Majorana fermions, single photon emitters, nanoprocessors, etc. The monolithic growth of site‐controlled nanowires is a prerequisite toward the next generation of devices that will require addressability and scalability. Here, combining top‐down nanofabrication and bottom‐up self‐assembly, the growth of Ge wires on prepatterned Si (001) substrates with controllable position, distance, length, and structure is reported. This is achieved by a novel growth process that uses a SiGe strain‐relaxation template and can be potentially generalized to other material combinations. Transport measurements show an electrically tunable spin–orbit coupling, with a spin–orbit length similar to that of III–V materials. Also, charge sensing between quantum dots in closely spaced wires is observed, which underlines their potential for the realization of advanced quantum devices. The reported results open a path toward scalable qubit devices using nanowires on silicon.}, author = {Gao, Fei and Wang, Jian-Huan and Watzinger, Hannes and Hu, Hao and Rančić, Marko J. and Zhang, Jie-Yin and Wang, Ting and Yao, Yuan and Wang, Gui-Lei and Kukucka, Josip and Vukušić, Lada and Kloeffel, Christoph and Loss, Daniel and Liu, Feng and Katsaros, Georgios and Zhang, Jian-Jun}, issn = {0935-9648}, journal = {Advanced Materials}, number = {16}, publisher = {Wiley}, title = {{Site-controlled uniform Ge/Si hut wires with electrically tunable spin-orbit coupling}}, doi = {10.1002/adma.201906523}, volume = {32}, year = {2020}, } @article{7546, abstract = {The extent to which behavior is shaped by experience varies between individuals. Genetic differences contribute to this variation, but the neural mechanisms are not understood. Here, we dissect natural variation in the behavioral flexibility of two Caenorhabditis elegans wild strains. In one strain, a memory of exposure to 21% O2 suppresses CO2-evoked locomotory arousal; in the other, CO2 evokes arousal regardless of previous O2 experience. We map that variation to a polymorphic dendritic scaffold protein, ARCP-1, expressed in sensory neurons. ARCP-1 binds the Ca2+-dependent phosphodiesterase PDE-1 and co-localizes PDE-1 with molecular sensors for CO2 at dendritic ends. Reducing ARCP-1 or PDE-1 activity promotes CO2 escape by altering neuropeptide expression in the BAG CO2 sensors. Variation in ARCP-1 alters behavioral plasticity in multiple paradigms. Our findings are reminiscent of genetic accommodation, an evolutionary process by which phenotypic flexibility in response to environmental variation is reset by genetic change.}, author = {Beets, Isabel and Zhang, Gaotian and Fenk, Lorenz A. and Chen, Changchun and Nelson, Geoffrey M. and Félix, Marie-Anne and de Bono, Mario}, issn = {0896-6273}, journal = {Neuron}, number = {1}, pages = {106--121.e10}, publisher = {Cell Press}, title = {{Natural variation in a dendritic scaffold protein remodels experience-dependent plasticity by altering neuropeptide expression}}, doi = {10.1016/j.neuron.2019.10.001}, volume = {105}, year = {2020}, } @article{7554, abstract = {Slicing a Voronoi tessellation in ${R}^n$ with a $k$-plane gives a $k$-dimensional weighted Voronoi tessellation, also known as a power diagram or Laguerre tessellation. Mapping every simplex of the dual weighted Delaunay mosaic to the radius of the smallest empty circumscribed sphere whose center lies in the $k$-plane gives a generalized discrete Morse function. Assuming the Voronoi tessellation is generated by a Poisson point process in ${R}^n$, we study the expected number of simplices in the $k$-dimensional weighted Delaunay mosaic as well as the expected number of intervals of the Morse function, both as functions of a radius threshold. As a by-product, we obtain a new proof for the expected number of connected components (clumps) in a line section of a circular Boolean model in ${R}^n$.}, author = {Edelsbrunner, Herbert and Nikitenko, Anton}, issn = {10957219}, journal = {Theory of Probability and its Applications}, number = {4}, pages = {595--614}, publisher = {SIAM}, title = {{Weighted Poisson–Delaunay mosaics}}, doi = {10.1137/S0040585X97T989726}, volume = {64}, year = {2020}, } @article{7563, abstract = {We introduce “state space persistence analysis” for deducing the symbolic dynamics of time series data obtained from high-dimensional chaotic attractors. To this end, we adapt a topological data analysis technique known as persistent homology for the characterization of state space projections of chaotic trajectories and periodic orbits. By comparing the shapes along a chaotic trajectory to those of the periodic orbits, state space persistence analysis quantifies the shape similarity of chaotic trajectory segments and periodic orbits. We demonstrate the method by applying it to the three-dimensional Rössler system and a 30-dimensional discretization of the Kuramoto–Sivashinsky partial differential equation in (1+1) dimensions. One way of studying chaotic attractors systematically is through their symbolic dynamics, in which one partitions the state space into qualitatively different regions and assigns a symbol to each such region.1–3 This yields a “coarse-grained” state space of the system, which can then be reduced to a Markov chain encoding all possible transitions between the states of the system. While it is possible to obtain the symbolic dynamics of low-dimensional chaotic systems with standard tools such as Poincaré maps, when applied to high-dimensional systems such as turbulent flows, these tools alone are not sufficient to determine symbolic dynamics.4,5 In this paper, we develop “state space persistence analysis” and demonstrate that it can be utilized to infer the symbolic dynamics in very high-dimensional settings.}, author = {Yalniz, Gökhan and Budanur, Nazmi B}, issn = {1089-7682}, journal = {Chaos}, number = {3}, publisher = {AIP Publishing}, title = {{Inferring symbolic dynamics of chaotic flows from persistence}}, doi = {10.1063/1.5122969}, volume = {30}, year = {2020}, } @article{7567, abstract = {Coxeter triangulations are triangulations of Euclidean space based on a single simplex. By this we mean that given an individual simplex we can recover the entire triangulation of Euclidean space by inductively reflecting in the faces of the simplex. In this paper we establish that the quality of the simplices in all Coxeter triangulations is O(1/d−−√) of the quality of regular simplex. We further investigate the Delaunay property for these triangulations. Moreover, we consider an extension of the Delaunay property, namely protection, which is a measure of non-degeneracy of a Delaunay triangulation. In particular, one family of Coxeter triangulations achieves the protection O(1/d2). We conjecture that both bounds are optimal for triangulations in Euclidean space.}, author = {Choudhary, Aruni and Kachanovich, Siargey and Wintraecken, Mathijs}, issn = {1661-8289}, journal = {Mathematics in Computer Science}, pages = {141--176}, publisher = {Springer Nature}, title = {{Coxeter triangulations have good quality}}, doi = {10.1007/s11786-020-00461-5}, volume = {14}, year = {2020}, } @article{7569, abstract = {Genes differ in the frequency at which they are expressed and in the form of regulation used to control their activity. In particular, positive or negative regulation can lead to activation of a gene in response to an external signal. Previous works proposed that the form of regulation of a gene correlates with its frequency of usage: positive regulation when the gene is frequently expressed and negative regulation when infrequently expressed. Such network design means that, in the absence of their regulators, the genes are found in their least required activity state, hence regulatory intervention is often necessary. Due to the multitude of genes and regulators, spurious binding and unbinding events, called “crosstalk”, could occur. To determine how the form of regulation affects the global crosstalk in the network, we used a mathematical model that includes multiple regulators and multiple target genes. We found that crosstalk depends non-monotonically on the availability of regulators. Our analysis showed that excess use of regulation entailed by the formerly suggested network design caused high crosstalk levels in a large part of the parameter space. We therefore considered the opposite ‘idle’ design, where the default unregulated state of genes is their frequently required activity state. We found, that ‘idle’ design minimized the use of regulation and thus minimized crosstalk. In addition, we estimated global crosstalk of S. cerevisiae using transcription factors binding data. We demonstrated that even partial network data could suffice to estimate its global crosstalk, suggesting its applicability to additional organisms. We found that S. cerevisiae estimated crosstalk is lower than that of a random network, suggesting that natural selection reduces crosstalk. In summary, our study highlights a new type of protein production cost which is typically overlooked: that of regulatory interference caused by the presence of excess regulators in the cell. It demonstrates the importance of whole-network descriptions, which could show effects missed by single-gene models.}, author = {Grah, Rok and Friedlander, Tamar}, issn = {1553-7358}, journal = {PLOS Computational Biology}, number = {2}, publisher = {Public Library of Science}, title = {{The relation between crosstalk and gene regulation form revisited}}, doi = {10.1371/journal.pcbi.1007642}, volume = {16}, year = {2020}, } @article{7570, abstract = {The relaxation of few-body quantum systems can strongly depend on the initial state when the system’s semiclassical phase space is mixed; i.e., regions of chaotic motion coexist with regular islands. In recent years, there has been much effort to understand the process of thermalization in strongly interacting quantum systems that often lack an obvious semiclassical limit. The time-dependent variational principle (TDVP) allows one to systematically derive an effective classical (nonlinear) dynamical system by projecting unitary many-body dynamics onto a manifold of weakly entangled variational states. We demonstrate that such dynamical systems generally possess mixed phase space. When TDVP errors are small, the mixed phase space leaves a footprint on the exact dynamics of the quantum model. For example, when the system is initialized in a state belonging to a stable periodic orbit or the surrounding regular region, it exhibits persistent many-body quantum revivals. As a proof of principle, we identify new types of “quantum many-body scars,” i.e., initial states that lead to long-time oscillations in a model of interacting Rydberg atoms in one and two dimensions. Intriguingly, the initial states that give rise to most robust revivals are typically entangled states. On the other hand, even when TDVP errors are large, as in the thermalizing tilted-field Ising model, initializing the system in a regular region of phase space leads to a surprising slowdown of thermalization. Our work establishes TDVP as a method for identifying interacting quantum systems with anomalous dynamics in arbitrary dimensions. Moreover, the mixed phase space classical variational equations allow one to find slowly thermalizing initial conditions in interacting models. Our results shed light on a link between classical and quantum chaos, pointing toward possible extensions of the classical Kolmogorov-Arnold-Moser theorem to quantum systems.}, author = {Michailidis, Alexios and Turner, C. J. and Papić, Z. and Abanin, D. A. and Serbyn, Maksym}, issn = {2160-3308}, journal = {Physical Review X}, number = {1}, publisher = {American Physical Society}, title = {{Slow quantum thermalization and many-body revivals from mixed phase space}}, doi = {10.1103/physrevx.10.011055}, volume = {10}, year = {2020}, } @inbook{7572, abstract = {The polymerization–depolymerization dynamics of cytoskeletal proteins play essential roles in the self-organization of cytoskeletal structures, in eukaryotic as well as prokaryotic cells. While advances in fluorescence microscopy and in vitro reconstitution experiments have helped to study the dynamic properties of these complex systems, methods that allow to collect and analyze large quantitative datasets of the underlying polymer dynamics are still missing. Here, we present a novel image analysis workflow to study polymerization dynamics of active filaments in a nonbiased, highly automated manner. Using treadmilling filaments of the bacterial tubulin FtsZ as an example, we demonstrate that our method is able to specifically detect, track and analyze growth and shrinkage of polymers, even in dense networks of filaments. We believe that this automated method can facilitate the analysis of a large variety of dynamic cytoskeletal systems, using standard time-lapse movies obtained from experiments in vitro as well as in the living cell. Moreover, we provide scripts implementing this method as supplementary material.}, author = {Dos Santos Caldas, Paulo R and Radler, Philipp and Sommer, Christoph M and Loose, Martin}, booktitle = {Methods in Cell Biology}, editor = {Tran, Phong }, issn = {0091679X}, pages = {145--161}, publisher = {Elsevier}, title = {{Computational analysis of filament polymerization dynamics in cytoskeletal networks}}, doi = {10.1016/bs.mcb.2020.01.006}, volume = {158}, year = {2020}, } @article{7573, abstract = {This paper deals with dynamical optimal transport metrics defined by spatial discretisation of the Benamou–Benamou formula for the Kantorovich metric . Such metrics appear naturally in discretisations of -gradient flow formulations for dissipative PDE. However, it has recently been shown that these metrics do not in general converge to , unless strong geometric constraints are imposed on the discrete mesh. In this paper we prove that, in a 1-dimensional periodic setting, discrete transport metrics converge to a limiting transport metric with a non-trivial effective mobility. This mobility depends sensitively on the geometry of the mesh and on the non-local mobility at the discrete level. Our result quantifies to what extent discrete transport can make use of microstructure in the mesh to reduce the cost of transport.}, author = {Gladbach, Peter and Kopfer, Eva and Maas, Jan and Portinale, Lorenzo}, issn = {00217824}, journal = {Journal de Mathematiques Pures et Appliquees}, number = {7}, pages = {204--234}, publisher = {Elsevier}, title = {{Homogenisation of one-dimensional discrete optimal transport}}, doi = {10.1016/j.matpur.2020.02.008}, volume = {139}, year = {2020}, } @article{7580, abstract = {The eukaryotic endomembrane system is controlled by small GTPases of the Rab family, which are activated at defined times and locations in a switch-like manner. While this switch is well understood for an individual protein, how regulatory networks produce intracellular activity patterns is currently not known. Here, we combine in vitro reconstitution experiments with computational modeling to study a minimal Rab5 activation network. We find that the molecular interactions in this system give rise to a positive feedback and bistable collective switching of Rab5. Furthermore, we find that switching near the critical point is intrinsically stochastic and provide evidence that controlling the inactive population of Rab5 on the membrane can shape the network response. Notably, we demonstrate that collective switching can spread on the membrane surface as a traveling wave of Rab5 activation. Together, our findings reveal how biochemical signaling networks control vesicle trafficking pathways and how their nonequilibrium properties define the spatiotemporal organization of the cell.}, author = {Bezeljak, Urban and Loya, Hrushikesh and Kaczmarek, Beata M and Saunders, Timothy E. and Loose, Martin}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {12}, pages = {6504--6549}, publisher = {Proceedings of the National Academy of Sciences}, title = {{Stochastic activation and bistability in a Rab GTPase regulatory network}}, doi = {10.1073/pnas.1921027117}, volume = {117}, year = {2020}, } @article{7582, abstract = {Small RNAs (smRNA, 19–25 nucleotides long), which are transcribed by RNA polymerase II, regulate the expression of genes involved in a multitude of processes in eukaryotes. miRNA biogenesis and the proteins involved in the biogenesis pathway differ across plant and animal lineages. The major proteins constituting the biogenesis pathway, namely, the Dicers (DCL/DCR) and Argonautes (AGOs), have been extensively studied. However, the accessory proteins (DAWDLE (DDL), SERRATE (SE), and TOUGH (TGH)) of the pathway that differs across the two lineages remain largely uncharacterized. We present the first detailed report on the molecular evolution and divergence of these proteins across eukaryotes. Although DDL is present in eukaryotes and prokaryotes, SE and TGH appear to be specific to eukaryotes. The addition/deletion of specific domains and/or domain-specific sequence divergence in the three proteins points to the observed functional divergence of these proteins across the two lineages, which correlates with the differences in miRNA length across the two lineages. Our data enhance the current understanding of the structure–function relationship of these proteins and reveals previous unexplored crucial residues in the three proteins that can be used as a basis for further functional characterization. The data presented here on the number of miRNAs in crown eukaryotic lineages are consistent with the notion of the expansion of the number of miRNA-coding genes in animal and plant lineages correlating with organismal complexity. Whether this difference in functionally correlates with the diversification (or presence/absence) of the three proteins studied here or the miRNA signaling in the plant and animal lineages is unclear. Based on our results of the three proteins studied here and previously available data concerning the evolution of miRNA genes in the plant and animal lineages, we believe that miRNAs probably evolved once in the ancestor to crown eukaryotes and have diversified independently in the eukaryotes.}, author = {Moturu, Taraka Ramji and Sinha, Sansrity and Salava, Hymavathi and Thula, Sravankumar and Nodzyński, Tomasz and Vařeková, Radka Svobodová and Friml, Jiří and Simon, Sibu}, issn = {22237747}, journal = {Plants}, number = {3}, publisher = {MDPI}, title = {{Molecular evolution and diversification of proteins involved in miRNA maturation pathway}}, doi = {10.3390/plants9030299}, volume = {9}, year = {2020}, } @article{7586, abstract = {CLC chloride/proton exchangers may support acidification of endolysosomes and raise their luminal Cl− concentration. Disruption of endosomal ClC‐3 causes severe neurodegeneration. To assess the importance of ClC‐3 Cl−/H+ exchange, we now generate Clcn3unc/unc mice in which ClC‐3 is converted into a Cl− channel. Unlike Clcn3−/− mice, Clcn3unc/unc mice appear normal owing to compensation by ClC‐4 with which ClC‐3 forms heteromers. ClC‐4 protein levels are strongly reduced in Clcn3−/−, but not in Clcn3unc/unc mice because ClC‐3unc binds and stabilizes ClC‐4 like wild‐type ClC‐3. Although mice lacking ClC‐4 appear healthy, its absence in Clcn3unc/unc/Clcn4−/− mice entails even stronger neurodegeneration than observed in Clcn3−/− mice. A fraction of ClC‐3 is found on synaptic vesicles, but miniature postsynaptic currents and synaptic vesicle acidification are not affected in Clcn3unc/unc or Clcn3−/− mice before neurodegeneration sets in. Both, Cl−/H+‐exchange activity and the stabilizing effect on ClC‐4, are central to the biological function of ClC‐3.}, author = {Weinert, Stefanie and Gimber, Niclas and Deuschel, Dorothea and Stuhlmann, Till and Puchkov, Dmytro and Farsi, Zohreh and Ludwig, Carmen F. and Novarino, Gaia and López-Cayuqueo, Karen I. and Planells-Cases, Rosa and Jentsch, Thomas J.}, issn = {14602075}, journal = {EMBO Journal}, publisher = {EMBO Press}, title = {{Uncoupling endosomal CLC chloride/proton exchange causes severe neurodegeneration}}, doi = {10.15252/embj.2019103358}, volume = {39}, year = {2020}, } @article{7593, abstract = {Heterozygous loss of human PAFAH1B1 (coding for LIS1) results in the disruption of neurogenesis and neuronal migration via dysregulation of microtubule (MT) stability and dynein motor function/localization that alters mitotic spindle orientation, chromosomal segregation, and nuclear migration. Recently, human induced pluripotent stem cell (iPSC) models revealed an important role for LIS1 in controlling the length of terminal cell divisions of outer radial glial (oRG) progenitors, suggesting cellular functions of LIS1 in regulating neural progenitor cell (NPC) daughter cell separation. Here we examined the late mitotic stages NPCs in vivo and mouse embryonic fibroblasts (MEFs) in vitro from Pafah1b1-deficient mutants. Pafah1b1-deficient neocortical NPCs and MEFs similarly exhibited cleavage plane displacement with mislocalization of furrow-associated markers, associated with actomyosin dysfunction and cell membrane hyper-contractility. Thus, it suggests LIS1 acts as a key molecular link connecting MTs/dynein and actomyosin, ensuring that cell membrane contractility is tightly controlled to execute proper daughter cell separation.}, author = {Moon, Hyang Mi and Hippenmeyer, Simon and Luo, Liqun and Wynshaw-Boris, Anthony}, issn = {2050-084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{LIS1 determines cleavage plane positioning by regulating actomyosin-mediated cell membrane contractility}}, doi = {10.7554/elife.51512}, volume = {9}, year = {2020}, } @article{7594, abstract = {The concept of the entanglement between spin and orbital degrees of freedom plays a crucial role in our understanding of various phases and exotic ground states in a broad class of materials, including orbitally ordered materials and spin liquids. We investigate how the spin-orbital entanglement in a Mott insulator depends on the value of the spin-orbit coupling of the relativistic origin. To this end, we numerically diagonalize a one-dimensional spin-orbital model with Kugel-Khomskii exchange interactions between spins and orbitals on different sites supplemented by the on-site spin-orbit coupling. In the regime of small spin-orbit coupling with regard to the spin-orbital exchange, the ground state to a large extent resembles the one obtained in the limit of vanishing spin-orbit coupling. On the other hand, for large spin-orbit coupling the ground state can, depending on the model parameters, either still show negligible spin-orbital entanglement or evolve to a highly spin-orbitally-entangled phase with completely distinct properties that are described by an effective XXZ model. The presented results suggest that (i) the spin-orbital entanglement may be induced by large on-site spin-orbit coupling, as found in the 5d transition metal oxides, such as the iridates; (ii) for Mott insulators with weak spin-orbit coupling of Ising type, such as, e.g., the alkali hyperoxides, the effects of the spin-orbit coupling on the ground state can, in the first order of perturbation theory, be neglected.}, author = {Gotfryd, Dorota and Paerschke, Ekaterina and Chaloupka, Jiri and Oles, Andrzej M. and Wohlfeld, Krzysztof}, journal = {Physical Review Research}, number = {1}, publisher = {American Physical Society}, title = {{How spin-orbital entanglement depends on the spin-orbit coupling in a Mott insulator}}, doi = {10.1103/PhysRevResearch.2.013353}, volume = {2}, year = {2020}, } @article{7600, abstract = {Directional intercellular transport of the phytohormone auxin mediated by PIN FORMED (PIN) efflux carriers plays essential roles in both coordinating patterning processes and integrating multiple external cues by rapidly redirecting auxin fluxes. Multilevel regulations of PIN activity under internal and external cues are complicated; however, the underlying molecular mechanism remains elusive. Here we demonstrate that 3’-Phosphoinositide-Dependent Protein Kinase1 (PDK1), which is conserved in plants and mammals, functions as a molecular hub integrating the upstream lipid signalling and the downstream substrate activity through phosphorylation. Genetic analysis uncovers that loss-of-function Arabidopsis mutant pdk1.1 pdk1.2 exhibits a plethora of abnormalities in organogenesis and growth, due to the defective PIN-dependent auxin transport. Further cellular and biochemical analyses reveal that PDK1 phosphorylates D6 Protein Kinase to facilitate its activity towards PIN proteins. Our studies establish a lipid-dependent phosphorylation cascade connecting membrane composition-based cellular signalling with plant growth and patterning by regulating morphogenetic auxin fluxes.}, author = {Tan, Shutang and Zhang, Xixi and Kong, Wei and Yang, Xiao-Li and Molnar, Gergely and Vondráková, Zuzana and Filepová, Roberta and Petrášek, Jan and Friml, Jiří and Xue, Hong-Wei}, issn = {20550278}, journal = {Nature Plants}, pages = {556--569}, publisher = {Springer Nature}, title = {{The lipid code-dependent phosphoswitch PDK1–D6PK activates PIN-mediated auxin efflux in Arabidopsis}}, doi = {10.1038/s41477-020-0648-9}, volume = {6}, year = {2020}, } @unpublished{7601, abstract = {Plasmodesmata (PD) are crucial structures for intercellular communication in multicellular plants with remorins being their crucial plant-specific structural and functional constituents. The PD biogenesis is an intriguing but poorly understood process. By expressing an Arabidopsis remorin protein in mammalian cells, we have reconstituted a PD-like filamentous structure, termed remorin filament (RF), connecting neighboring cells physically and physiologically. Notably, RFs are capable of transporting macromolecules intercellularly, in a way similar to plant PD. With further super-resolution microscopic analysis and biochemical characterization, we found that RFs are also composed of actin filaments, forming the core skeleton structure, aligned with the remorin protein. This unique heterologous filamentous structure might explain the molecular mechanism for remorin function as well as PD construction. Furthermore, remorin protein exhibits a specific distribution manner in the plasma membrane in mammalian cells, representing a lipid nanodomain, depending on its lipid modification status. Our studies not only provide crucial insights into the mechanism of PD biogenesis, but also uncovers unsuspected fundamental mechanistic and evolutionary links between intercellular communication systems of plants and animals.}, author = {Wei, Zhuang and Tan, Shutang and Liu, Tao and Wu, Yuan and Lei, Ji-Gang and Chen, ZhengJun and Friml, Jiří and Xue, Hong-Wei and Liao, Kan}, booktitle = {bioRxiv}, pages = {22}, publisher = {Cold Spring Harbor Laboratory}, title = {{Plasmodesmata-like intercellular connections by plant remorin in animal cells}}, doi = {10.1101/791137}, year = {2020}, } @article{7603, abstract = {Plants are exposed to a variety of abiotic and biotic stresses that may result in DNA damage. Endogenous processes - such as DNA replication, DNA recombination, respiration, or photosynthesis - are also a threat to DNA integrity. It is therefore essential to understand the strategies plants have developed for DNA damage detection, signaling, and repair. Alternative splicing (AS) is a key post-transcriptional process with a role in regulation of gene expression. Recent studies demonstrate that the majority of intron-containing genes in plants are alternatively spliced, highlighting the importance of AS in plant development and stress response. Not only does AS ensure a versatile proteome and influence the abundance and availability of proteins greatly, it has also emerged as an important player in the DNA damage response (DDR) in animals. Despite extensive studies of DDR carried out in plants, its regulation at the level of AS has not been comprehensively addressed. Here, we provide some insights into the interplay between AS and DDR in plants.}, author = {Nimeth, Barbara Anna and Riegler, Stefan and Kalyna, Maria}, issn = {1664462X}, journal = {Frontiers in Plant Science}, publisher = {Frontiers}, title = {{Alternative splicing and DNA damage response in plants}}, doi = {10.3389/fpls.2020.00091}, volume = {11}, year = {2020}, }